3
EPIDEMIOLOGY CUP constitutes 2-4% of all malignacies Annual age-adjusted incidence in US is 7-12 cases per 100,000 population Median age at presentation is 60 years Slightly more prevalent in males 5-10% of case are characterized by a relatively favourable prognosis

6
TREATMENT UNFAVORABLE SUBSETS With the exception of the favorable subsets, most patients with CUP have a tumor that is resistant to chemotherapy The prognosis is very poor, with median survival of 2 to 3 months in unselected patients and 6 to 10 months in those enrolled into clinical trials Patients with good performance status may benefit from systemic chemotherapy

7
Chemotherapy for unfavorable subsets Open Questions Which chemotherapy regimen? Is the combination of Platinum and Taxane the standard of care? Is there any role for a third agent?

14
CONCLUSIONS Clinical trials evaluated a group of heterogeneous tumors sharing the unique characteristic of metastatic disease without identifiable origin at the time of initial therapy Only phase II trials, few randomized No randomized phase III trials designed to establish the efficacy of combination chemotherapy over BSC or Platinum single agent Among unfavourable subsets, patients with good performance status may benefit from systemic chemotherapy There is no chemotherapy of choice although the most commonly used regimens use the combination of a platinum and a taxane The role for a third agent such as gemcitabine, irinotecan or etoposide remains unclear

18
Comparative survival with diverse chemotherapy regimens for cancer of unknown primary site: Multiple-treatments meta-analysis Golfinopoulos et al, 2009 Multiple-treatments meta-analysis showed no significant benefit for any treatment group over others No type of chemotherapy has been solidly proven to prolong survival in patients with CUP Regimens using either platinum or taxanes or both show some trends for prolongation of survival, but the data a limited. Taxane regimens seem to have the best results Median OS is 8-12 months for the trial published after the year 2000, but this gain may not necessary depend on systemic chemotherapy A taxane/platimun combination may prolong survival by 1.5 months BSC may be considered for old or unfit unfavorable CUP

29
Phase II trial which evaluated the combined inhibition of VEGF and EGFR with bevacizumab and erlotinib. Patients who either had received previous chemotherapy or were previously untreated with poor- prognosis clinical features. All patients received bevacizumab 10 mg/kg every 2 weeks, along with erlotinib 150 mg orally daily. 47/51 patients received at least 8 weeks of treatment. 10% PR, 61% SD Median survival for the entire group was 7.4 months, with 33% of patients alive at 1 year. This regimen was well tolerated by most patients.

33
CUPL is an unfavourable subset of cancer of unknown primary site Male/female ratio 2:1. Median age at diagnosis: 61–65. Lung, pancreatic and colorectal primary tumors are most commonly identified in the setting of CUP patients presenting with liver metastases The most commonly involved metastatic sites in addition to hepatic involvement are lymph nodes, bone and lung. Adenocarcinoma is the prevalent histology (64%), followed by undifferentiated carcinoma (20%), neurondocrine (8.4%) and squamous (3%). Liver Metastasis subgroup

40
TREATMENT FAVORABLE SUBSETS 2. Women with papillary serous adenocarcinoma of the peritoneal cavity The germinal epithelium of the ovary and peritoneal mesothelium share the same embryological origin More common in women with BRCA-1 mutation and may also be seen after prophylactic oophorectomy Outcomes are similar to ovarian cancer at equivalent stage Patients should be treated as stage III ovarian carcinoma Surgical debulking followed by chemotherapy

41
TREATMENT FAVORABLE SUBSETS 3. Squamous cell carcinoma of the cervical lymph nodes Despite aggressive diagnostic approach, the primary site is not found in the majority of patients Ipsilateral tonsilectomy is often performed since the primary can be found in 10 to 25% of cases - Small tumors may originate in the deep crypts and not be detected by superficial biopsy Treat as locally advanced head and neck cancer Low stage (N1) – Surgery  RT or RT alone High stage (N2-N3) - Chemoradiotherapy

42
TREATMENT FAVORABLE SUBSETS 4. Isolated inguinal squamous cell carcinoma Tumor is usually located in the genital or anorectal area Patients without an identifiable primary tumor may benefit from inguinal lymphadenectomy, with or without adjuvant radiation therapy The role for chemotherapy in the adjuvant setting is not well defined Surgery ± RT, ? chemotherapy

46
TREATMENT FAVORABLE SUBSETS 8. Single metastatic site Although other metastatic sites may become evident within a short period, some patients may achieve a prolonged disease- free interval with local therapies such as surgery or radiotherapy Adjuvant chemotherapy may also be considered Surgery or RT

47
CONCLUSIONS Potential roles for DNA microarray technology 1.Identify the primary site 2.Identify clinically relevant subsets of tumors with similar gene expression profiles 3.Identify specific and novel targets for treatment Targeted therapies such as EGFR inhibitors and anti- angiogenesis agents may have a role in the treatment of CUP, particularly in patients with unfavorable subsets –PR 10%, SD 61%, Median survival 7.4 months in 2 nd line –RR 53%, PFS 8 months, median survival 12.6 months in 1 st line

About project

Feedback

To ensure the functioning of the site, we use cookies. We share information about your activities on the site with our partners and Google partners: social networks and companies engaged in advertising and web analytics. For more information, see the Privacy Policy and Google Privacy &amp Terms.
Your consent to our cookies if you continue to use this website.